An aim of modern medicine is to provide personalized or individualized treatment regimens. Those are treatment regimens which take into account a patient's individual needs or risks. Personalized or individual treatment regimens shall be also taken into account for emergency measures. Specifically, in the case of acute cardiovascular events, a decision for a certain treatment regimen must be made, usually, within a short period of time. Cardiovascular complications, particularly heart diseases, are the leading cause of morbidity and mortality in the Western hemisphere. Cardiovascular complications can remain asymptomatic for long periods of time. However, they may have severe consequences once an acute cardiovascular event, such as myocardial infarction, as a cause of the cardiovascular complication occurs.
The conventional diagnostic techniques for cardiovascular complications include electrocardiographic and echocardiographic measurements, analysis of symptoms and previous medical history of the patient, such as chest pain, and analysis of some clinical parameters. Recently, these conventional techniques have been further strengthened by the analysis of biomarkers and, in particular, by the analysis of the levels for cardiac troponins in blood samples of emergency patients. Moreover, natriuretic peptides are also described as suitable biomarkers for diagnosing cardiovascular complications. Even more recently, GDF-15 has been suggested to be an indicator for cardiovascular complications, too (US2003/0232385; Kempf 2006, Circ Res 98: 351-360). Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β cytokine superfamily. GDF-15 was first identified as macrophage-inhibitory cytokine-1 (MIC-1), and later also named placental transforming growth factor-β (Bootcov 1997, Proc Natl Acad Sci 94:11514-11519; Tan 2000, Proc Natl Acad Sci 97:109-114). It has recently been shown that cultured cardiomyocytes express and secrete GDF-15 via nitric oxide and nitrosative stress-dependent signaling pathways when subjected to simulated ischemia and reperfusion. Moreover, it has been observed in a mouse model of myocardial ischemia and reperfusion injury that GDF-15 expression levels rapidly increase in the ischemic area following coronary artery ligation, and remain elevated in the reperfused myocardium for several days (Kempf loc. cit).
The conventional diagnostic techniques, specifically for emergency situations, usually do not allow for a reliable diagnosis and/or risk assessment. Thus, based on said diagnostic techniques, a personalized treatment regimen can not be determined with sufficient accuracy. As a consequence thereof, many patients will receive a treatment regimen which is insufficient or which may have adverse side effects. In many cases, acute cardiovascular events, once determined by the conventional diagnostic techniques referred to above and/or by troponin levels of the patient, are currently treated by cardiac interventions. Those cardiac interventions include various types of angioplasty-based interventions and/or coronary bypass surgery which are carried out in order to restore proper blood flow, e.g., within the coronary vessels. However, those interventions are not always successful and may be even harmful for the patient. In addition, the interventions are time and cost expensive. The same difficulties and deficiencies of current risk assessment techniques arise for interventions in patients with heart failure, e.g., drug therapies, such as treatment with an angiotensin converting enzyme inhibitor, angiotensin receptor blocker, beta-blocker, or aldosterone-antagonist, and interventional therapies, such as cardiac resynchronisation therapy (CRT) or the implantable cardioverter-defibrillator (ICD).
Therefore, there is a need for diagnostic or prognostic measures which allow an individual risk stratification for a patient who is suspected to be in need for a certain treatment regimen such as a cardiac intervention. Furthermore, there is a need for a reliable general risk stratification including the risk for mortality or recurrent adverse cardiovascular events in patients suffering from a cardiovascular complication and, especially, in patients exhibiting an acute cardiovascular event or heart failure.
The technical problem underlying the present invention can be seen as the provision of means and methods for complying with the aforementioned needs.
The technical problem is solved by the embodiments characterized in the claims and herein below.